This proposal is for the addition of a Thermo Scientific LTQ Orbitrap Velos ETD hybrid FT mass spectrometer to the Mass Spectrometry Facility at the Medical University of South Carolina. The facility has a 39 year history of offerin state of the art mass spectrometry capability advancing a wide range of biomedical research interests in the local research community. Over the past three years, the facility has provided mass spectrometric analysis and assistance to 77 different faculty investigators within the university and multiple NIH-funded investigators at other institutions. The most highly requested services offered by the facility are protein identification and the characterization of posttranslational modifications. For these purposes, the most heavily used instruments in the facility are the low resolution linear ion trap mass spectrometers. The facility lacks an instrumen with the combined sensitivity, resolution, and multiple modes of peptide fragmentation that are achievable with the LTQ Orbitrap Velos ETD mass spectrometer. In fact, there is not an Orbitrap mass analyzer in South Carolina. The improved mass accuracy of this instrument will provide a higher level of confidence in peptide and protein identifications and in the site-assignment of posttranslational modifications (PTMs). Combining multiple fragmentation options (CID, HCD, ETD) with high mass accuracy measurements will enable quantitative approaches aimed at simultaneous identification and quantitation of protein modifications, a capability which is not currently available to facility users. The ETD ionization source accessory will 1) aid in projects requiring the characterization of PTMs and de novo sequencing and 2) provide new capabilities enabling top to middle-down protein analysis and quantitation of modifications that are destroyed during CID. The requested instrument will serve a representative group of Major Users including eleven NIH-funded investigators conducting research in the areas of cancer, cardiovascular disease, diabetes, vision, osteoporosis, and kidney disease. The Orbitrap Velos ETD instrument incorporates two mass analyzers and multiple fragmentation strategies yielding a powerful and very versatile instrument that will be well suited to address the broad range of protein analyses and characterization requested by investigators at MUSC and the neighboring universities and research centers in South Carolina. PUBLIC HEALTH RELEVANCE: The analysis of proteins by mass spectrometry is a fundamental analytical method utilized in biomedical research aimed at understanding processes underlying the onset and progression of disease and developing new therapeutics and diagnostics. The requested instrumentation will enhance our ability to identify and monitor changes in protein expression and regulatory post-translational modifications thereby advancing research in multiple areas including cancer, cardiovascular disease, diabetes, blindness, neurological disease, and osteoporosis.